Naproxen anti-inflammatory properties

Naproxen, (S)-6-Methoxy-a-methyl-2-naphthaleneacetic acid, is a popular anti-inflammatory, analgesic and antipyretic drug which is also used in veterinary medicine largely for its anti-inflammatory properties. Its structure is as follows ... 

Also other members of the profen-family, among them naproxen, flurbiprofen, ketoprofen and tiaprofenic acid, are of great importance today. In general, these are 2-aryl- or 2-heteroaryl-propionic acids, of which in vitro only the (S)-(+)-enantiomer inhibits cyclooxygenase-1 (Fig. 5.84). In vivo, depending on the particular animal species, and also in humans, the (U)-(-)-enantiomer is converted to various degrees into its (S)-enantiomer with the aid of -methylacyl-CoA-racemase, via the Coenzyme A-thioester. In addition, more recent investigations could show that (R)-ibuprofen and (R)-flurbiprofen themselves have also anti-inflammatory properties. Many of the profens, with the exception of naproxen, are therefore marketed as racemates. 

Naproxen is one of many drugs in the group classified as nonsteroidal anti-inflammatory drugs (NSAIDs). Naproxen is in the chemical class of propionic acid derivatives and possesses analgesic, antipyretic, and anti-inflammatory properties. It was first introduced in 1976 under the trade name Naprosyn by Roche Pharmaceuticals. Both the acid and salt formulations are currently used, with the salt form having a slightly more rapid absorption rate. Reduced-dose naproxen sodium was approved as an over-the-coimter (OTC) pain reliever in the USA in 1994 and entered the market under the trade name of Afleve [1,2]. 

As previously mentioned, the action of anti-inflammatory steroids stems from their ability to prevent the release of arachidonic acid. There is another class of therapeutic agents that also exhibit anti-inflammatory properties, but their mode of action is entirely different. These drugs are called non steroidal anti-inflammatory drugs, or NSAIDs, and the most common examples are aspirin, ibuprofen, and naproxen. 

Considerable effort has been directed towards the catalytic addition of HCN to vinylarenes since this represents a route to 2-arylpropionic acids, well-known anti-inflammatory agents.75 High levels of asymmetric induction are required (R)-naproxen has undesirable properties associated with it and only the ([Pg.277]

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory dmgs (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by hydroxycarbonylation [51,53] (several more listed in [52]). The carbonylation of styrene itself serves as a useful test reaction in order to learn the properties of new catalytic systems, such as activity, selectivity to acids, regioselectivity (1/b ratio) and enantioselectivity (e.e.) in the branched product. In aqueous or in aqueous/organic biphasic systems complexes of palladium were studied exclusively, and the results are summarized in Table 5.2. 

S)-Naproxen is the aaive ingredient in the widely used pain relievers Naprosyn and Aleve. The three-dimensional orientation of two atoms at a single carbon in naproxen determines its therapeutic properties. Changing the position of these two atoms converts this anti-inflammatory agent into a liver toxin. In Chapter 5 we learn more about stereochemistry and how small structural differences can have a large effect on the properties of a molecule. 

How differences in the three-dimensional structure of starch and cellulose affect their shape and function (Section 5.1) The three-dimensional structure of thalidomide, the anti-nausea dmg that caused catastrophic birth defects (Section 5.5) How mirror image isomers can have drastically different properties— the analgesic ibuprofen, the antidepressant fluoxetine, and the anti-inflammatory agent naproxen (Section 5.13)... 

All compounds of the test dataset are nonsteroidal anti-inflammatory drugs (NSAIDs) and are thus relatively similar in terms of their pharmacological properties (Fig. 18). The compounds are 1, acetylsalicylic acid 2, diclofenac 3, flufe-namic acid 4, flubiprofen 5, ibuprofen 6, indometacin 7, ketoprofen 8, meclofe-namic acid 9, mefenamic acid 10, naproxen 11, piroxicam 12, sulindac sulfide (active metabolite of sulindac) 13, tenoxicam 14, meloxicam 15, cgp 28238 16, DuP-697 17, L-745-337 18, 6-methoxy-2-naphthylacetic acid (active metabolite of nabumeton) 19, NS-389 20, SC 58125. 

Naproxen, a nonsteroidal anti-inflammatory drug, is practically insoluble in water. F or pharmaceutical application, improvement in the dissolution properties has been expected. Dissolution properties of naproxen in the JP first fluid (pH 1.2) were studied according to the JP paddle method (Fig. 8) [18]. A mixture with CPG 120 showed a dissolution curve similar to that of intact naproxen erystals. It is noteworthy that the dissolution of naproxen was significantly improved in the heated sample with CPG 120, especially in the initial stage of dissolution. In... 

M How mirror image isomers can have drastically different properties—the analgesic ibuprofen, the antidepressant fluoxetine, and the anti-inflammatory agent naproxen (Section 5.13)... 

---